It is known that the cell mediated immunity, particularly a cytotoxic T cell (hereinafter, referred to as “CTL”) plays a significant role in vivo rejection of tumor cells or viral infection cells. CTLs recognize a complex between a tumor antigen peptide and a major histocompatibility complex class I antigen, i.e., MHC class I antigen, which is referred to as “HLA antigen” in the case of human, on the cell surface of tumor cells, and attack and kill the cells.
Tumor antigen peptides are generated through the intracellular processing of intracellularly synthesized proteins specific for tumors (tumor antigen proteins) and degradated by proteases. The resultant tumor antigen peptides form a complex with MHC class I antigens (HLA antigens) in endoplasmic reticulum and transported to the cell surface where said complex is presented as an antigen. CTLs, when recognize the complex presented as an antigen, exhibit the anti-tumor effects through cytotoxic action or production of lymphokines. As a consequence of elucidation of a series of such actions, a therapy of tumor patients has become available, wherein a tumor antigen protein or peptide is administered as an immunotherapeutic agent, i.e., cancer vaccine, thereby enhancing tumor-specific CTLs in the patient.
Typical examples of tumor antigen proteins include those described in Immunity, 10: 281, 1999, Table 1. Specific examples include melanosome antigens such as melanocyte tissue specific proteins, for instance, gp100 (J. Exp. Med., 179:1005, 1994), MART-1 (Proc. Natl. Acad. Sci. USA, 91:3515, 1994) and melanosome proteins such as tyrosinase (J. Exp. Med., 178:489, 1993). Examples of tumor antigen proteins other than melanoma include HER2/neu (J. Exp. Med., 181: 2109, 1995), CEA (J. Natl. Cancer. Inst., 87: 982, 1995), and PSA (J. Natl. Cancer. Inst., 89: 293, 1997), etc. However, tumor antigen proteins broadly applicable to cancers (tumors) including sarcomas such as osteosarcoma have not been reported yet.
Papillomavirus binding factor (PBF, GenBank data base Accession No. AF263928) has been identified as a factor recognizing the E2 binding site of papillomavirus (Virology 293, 103-117, 2002). However, nothing has been known about the relationships between the PBF and tumors.